SRSF1 is essential for primary follicle development by regulating granulosa cell survival via mRNA alternative

Xiaohong Yao1, Chaofan Wang1, Weiran Yu1

  • 1State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.

Insights

Serine/arginine-rich splicing factor 1 (SRSF1) in granulosa cells is crucial for female reproduction. Its regulation of DNA repair genes impacts follicular development and prevents premature ovarian insufficiency.

Area of Science:

  • Reproductive biology
  • Molecular genetics
  • Cellular biology

Background:

  • Granulosa cell abnormalities are linked to premature ovarian insufficiency (POI).
  • The function of serine/arginine-rich splicing factor 1 (SRSF1) in mouse granulosa cells is not well understood.
  • SRSF1 is known to be involved in various diseases when abnormally expressed.

Purpose of the Study:

  • To investigate the role of SRSF1 in mouse granulosa cells.
  • To determine the impact of SRSF1 knockout in granulosa cells on follicular development and female reproduction.

Main Methods:

  • Specific knockout of Srsf1 in mouse granulosa cells.
  • RNA sequencing (RNA-seq) for gene expression analysis.
  • Gene Ontology (GO) and Alternative Splicing (AS) analyses.

Main Results:

  • SRSF1 knockout in granulosa cells inhibited follicular development, reduced cell proliferation, and increased apoptosis.
  • RNA-seq revealed altered expression of genes involved in DNA repair and cell signaling pathways.
  • SRSF1 regulates alternative splicing of DNA repair genes, impacting DNA damage in granulosa cells.

Conclusions:

  • SRSF1 in granulosa cells is essential for normal follicular development.
  • SRSF1 controls female reproduction by regulating alternative splicing of DNA repair genes.
  • Targeting SRSF1 may offer therapeutic strategies for reproductive disorders.

Related Concept Videos

RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
56.4K
Folliculogenesis01:20

Folliculogenesis

Folliculogenesis is the development of ovarian follicles, the specialized structures within the ovarian cortex where oogenesis, or egg development, occurs. This process is essential for female reproductive health and begins during fetal development when primordial follicles are formed. Each primordial follicle comprises a primary oocyte in the center, surrounded by a single layer of squamous pre-granulosa cells. These follicles remain dormant in late prophase I of meiosis until triggered by...
812
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.2K
Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
7.0K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
What is Gene Expression?01:36

What is Gene Expression?

A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised  of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
8.5K